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The Role of the Microenvironment in Barrett's Esophagus

Award Number: U54CA163004
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/26/2011
PERIOD OF PERFORMANCE END DATE: 10/31/2024

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The Role of the Microenvironment in Barrett's Esophagus - OVERALL PROJECT SUMMARY Barrett’s esophagus is an increasingly prevalent, preneoplastic disorder resulting from acid/bile reflux and chronic inflammation at the GE junction. This application is a renewal of a long-standing multicenter, translational research program from Columbia University, the University of Pennsylvania and the Mayo Clinic. The team, which has been highly productive, will now focus on the role of microbiota and the tumor microenvironment in the development and progression of Barrett’s esophagus and esophageal adenocarcinoma. The group has added additional collaborative sites at MIT, the Dana Farber Cancer Institute and Munich Technical University, and will utilize heavily a new Microbiome and Metabolomics Core at Penn- CHOP. Thus, the team comprises broad and unique expertise in mouse models, genomics, microbiology and clinical research. The application is built around the hypothesis that the inflammation-dependent tumor microenvironment, modulated by the GE junction microbiome, is critical for early progression of esophageal carcinogenesis. The proposal will utilize both the novel transgenic (L2-IL-1β) and innovative 3D organoid models, along with a cross-sectional study of 100 BE patients. Project 1 will study the role of microbiota and myeloid cells in the L2-IL-1β mouse model of Barrett’s esophagus. This project will incorporate germ-free housing, antibiotic eradication, colonization with defined flora, myeloid cell ablation and correlative human studies. Project 2 is focused on the characterization of microenvironment drivers in BE, and will include FACS/IHC analysis of CAFs and immune cells (MDSCs/Tregs) in BE patients, along with 3D organoids in culture. The role of IL-6 in response to epithelial TP53 mutations and immune cell activation will be defined. Finally, Project 3 will seek to identify novel biomarkers and gene signatures related to the microbiome and microenvironment. The study will analyze bile acids, a product of microbes, and minimally invasive tests such as saliva/breath test/tethered capsule sponge to analyze microbes to develop screening/surveillance strategies. Overall, these projects will advance the science of the microbiome and microenvironment in BE that will hopefully lead to translational applications.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$72 )
2025	2021	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	10	3/20/2025	NON-COMPETING CONTINUATION	-$72
														Subtotal = -$72

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	10	1/31/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	001	10	1/24/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	10	1/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $441,975 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	001	10	5/31/2022	SUPPLEMENT FOR EXPANSION	$441,975
2022	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	10	11/18/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $441,975

Issue Date FY: 2021 ( Subtotal = $1,145,406 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	001	10	4/29/2021	NON-COMPETING CONTINUATION	$1,145,406
2021	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	9	12/24/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,145,406

Issue Date FY: 2020 ( Subtotal = $964,412 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	001	9	8/21/2020	SUPPLEMENT FOR EXPANSION	$162,000
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	9	6/5/2020	NON-COMPETING CONTINUATION	$802,412
														Subtotal = $964,412

Issue Date FY: 2019 ( Subtotal = $1,288,641 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	001	8	7/15/2019	NON-COMPETING CONTINUATION	$149,999
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	8	6/14/2019	NON-COMPETING CONTINUATION	$1,138,642
														Subtotal = $1,288,641

Issue Date FY: 2018 ( Subtotal = $1,178,302 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	002	7	7/31/2018	NON-COMPETING CONTINUATION	$145,484
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	001	7	7/6/2018	SUPPLEMENT FOR EXPANSION	$93,257
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	7	5/25/2018	NON-COMPETING CONTINUATION	$939,561
														Subtotal = $1,178,302

Issue Date FY: 2017 ( Subtotal = $1,310,083 )
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	006	6	9/15/2017	COMPETING CONTINUATION	$290,014
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	000	6	5/12/2017	COMPETING CONTINUATION	$1,310,083
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	001	6	8/30/2017	COMPETING CONTINUATION	-$1,310,083
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	002	6	9/5/2017	COMPETING CONTINUATION	$1,310,083
2017	2016	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	005	5	9/14/2017	SUPPLEMENT FOR EXPANSION	$242,795
2017	2016	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	007	5	9/15/2017	SUPPLEMENT FOR EXPANSION	-$290,014
2017	2015	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	004	5	9/14/2017	SUPPLEMENT FOR EXPANSION	-$174,160
2017	2015	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Cancer Centers Support Grants	003	5	9/14/2017	NON-COMPETING CONTINUATION	-$68,635
														Subtotal = $1,310,083

Issue Date FY: 2016 ( Subtotal = $236,993 )
2016	2016	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	000	5	9/13/2016	SUPPLEMENT FOR EXPANSION	$236,993
2016	2015	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	001	5	9/16/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $236,993

Issue Date FY: 2015 ( Subtotal = $1,139,300 )
2015	2015	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	000	5	8/13/2015	NON-COMPETING CONTINUATION	$965,140
2015	2015	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	001	5	8/14/2015	SUPPLEMENT FOR EXPANSION	$174,160
														Subtotal = $1,139,300

Issue Date FY: 2014 ( Subtotal = $1,378,757 )
2014	2014	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	000	4	8/6/2014	NON-COMPETING CONTINUATION	$1,204,597
2014	2014	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	001	4	9/17/2014	SUPPLEMENT FOR EXPANSION	$174,160
														Subtotal = $1,378,757

Issue Date FY: 2013 ( Subtotal = $1,061,716 )
2013	2013	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW Memorial LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	000	3	9/9/2013	NON-COMPETING CONTINUATION	$1,061,716
														Subtotal = $1,061,716

Issue Date FY: 2012 ( Subtotal = $1,140,528 )
2012	2012	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW Memorial LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	000	2	8/23/2012	NON-COMPETING CONTINUATION	$1,140,528
														Subtotal = $1,140,528

Issue Date FY: 2011 ( Subtotal = $1,172,622 )
2011	2011	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW Memorial LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Cancer Centers Support Grants	000	1	9/27/2011	NEW	$1,172,622
														Subtotal = $1,172,622

Grand Total All Awards = $12,458,663

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The Role of the Microenvironment in Barrett's Esophagus

Award Number: U54CA163004

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/26/2011

PERIOD OF PERFORMANCE END DATE: 10/31/2024

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